The present invention relates generally to stents that are implantable or deployable in a vessel or duct within the body of a patient to maintain the lumen of the duct or vessel open, and more particularly to improvements in stent structures.
When inserted and deployed in a vessel, duct or tract of the body, for example a coronary artery after dilatation of the artery by balloon angioplasty, a stent acts as a prosthesis to maintain the vessel, duct or tract (generally referred to as a vessel for convenience herein) open. The stent has the form of an open-ended tubular element with openings through its sidewall to enable its expansion from a first outside diameter which is sufficiently small to allow it to be navigated through the vessel to a target site where it is to be deployed, to a deployed second outside diameter sufficiently large to engage the inner lining of the vessel for retention at the target site.
An occluded coronary artery, for example, is typically attributable to a buildup of fatty deposits or plaque on the inner lining of the vessel. A balloon angioplasty procedure is the treatment of choice to compress the deposits against the inner lining of the vessel to open the lumen. Alternatively, removal of plaque may be achieved by laser angioplasty, or by rotationally cutting the material into finely divided particles which are dispersed in the blood stream. For a large segment of patients undergoing the procedure, traditional angioplasty has resulted in new blockage of the treated vessel only a relatively short time thereafter, attributable to trauma to the blood vessel wall from the original procedure. The mechanism responsible for this restenosis or re-occlusion of the vessel lumen is intimal hyperplasia, a rapid proliferation of smooth muscle cells in the affected region of the wall.
To maintain the vessel open, it has become customary to install a stent at the trauma site at the time of or shortly after the angioplasty procedure is performed. The stent is deployed by radial expansion under outwardly directed radial pressure exerted, for example, by active inflation of a balloon of a balloon catheter on which the stent is mounted. In some instances, passive spring characteristics of a pre-formed elastic (i.e., self-opening) stent serves the purpose. The stent is thus expanded to engage the inner lining or inwardly facing surface of the vessel wall with sufficient resilience to allow some contraction but also with sufficient stiffness to largely resist the natural recoil of the vessel wall.
The presence of the stent in the vessel, however, tends to promote thrombus formation as blood flows through the vessel, which results in an acute blockage. The thrombosis and clotting may be reduced or even eliminated by appropriate surface characteristics of the stent, sufficient to achieve this purpose. At the outward facing surface of the stent in contact or engagement with the inner lining of the vessel, tissue irritation can exacerbate restenosis attributable to hyperplasia.
Another factor affecting the choice of the stent and the stent material is allergic reaction to common stent materials suffered by a statistically significant percentage of the patient population subjected to stenting. These materials include chrome, nickel, and medical grade 316L stainless steel, which contains about 16% nickel. For such patients, the allergic reaction may be sufficient that stent implant is contraindicated. Wholly biodegradable stents of possibly sufficient radial strength are currently undergoing tests and may prove suitable in such cases.
Another consideration in material selection is the need for the implanting physician to be able to visualize the position of the stent during implantation to the desired target site in the body, and for purposes of examination from time to time thereafter at the implant site, typically by x-ray fluoroscopy. The wall of the stent must be sufficiently thick, depending on the stent material, not only to withstand the vessel wall recoil that invariably follows deployment at the target site, but to allow the stent to be seen on the fluoroscope. Various materials, such as 316L stainless steel, possess suitable mechanical strength. Typical stent wall or wire thicknesses have ranged from 70 to 200 microns (or micrometers, μm). A 70 to 80 μm thick 316L steel stent offers sufficient strength to resist recoil so as to maintain a lumen diameter close to the diameter achieved at full deployment by balloon inflation. This relatively thin and tiny metal structure creates little shadow on a fluoroscopic picture, however, since the x-ray absorption of the metal is low. Increasing the wall thickness of the stent to enhance its radiopacity and recoil resistance makes the stent less flexible, however, which adversely affects its maneuverability through narrow vessels and the amount of balloon pressurization necessary to enlarge the stent diameter sufficiently during deployment, with concomitant increased risk of balloon rupture.
It follows that a suitable stent for successful interventional placement should possess features of relatively non-allergenic reaction, good radiopacity, freedom from distortion on magnetic resonance imaging (MRI), flexibility with suitable elasticity to be plastically deformable, resistance to vessel recoil, sufficient thinness to minimize obstruction to flow of blood (or other fluid or material in vessels other than the cardiovascular system), and biocompatibility to avoid of vessel re-occlusion. Selection of the stent material, as well as design of the stent, plays an important role in influencing these features.
Aside from vascular usage, other ducts or tracts of the human body in which a stent might be installed to maintain an open lumen include the tracheo-bronchial system, the biliary hepatic system, the esophageal bowel system, and the urinary tract. Many of the same requirements are found in these other endoluminal usages of stents.
Despite improvements in the design and construction of coronary stents, restenosis remains a problem. A major contributing factor is the inability of the body to incorporate the implanted foreign material quickly. Basic research with cell cultures and animal experiments have demonstrated that the degree of endothelialization of the foreign body determines the amount of the restenosis. It has been an assumption among industry practitioners and researchers that a highly polished and smooth surface is beneficial to prevent stent thrombosis and to facilitate endothelialization, but experiments indicate this may not be entirely true.
A significant reason for the lack of a high clinical success rate with electropolished stents is the fact that the smooth muscle cells which seek to envelop a foreign body, such as a stent strut into the vessel wall, require a higher degree of proliferation to cover the foreign body. The continuing flow of blood with a high pressure and high shearing stress prevents the migration of smooth muscle cells, which proliferate from the media and adventitial cells of a stented vessel such as a coronary artery. It has been shown that a slightly rough surface considerably facilitates the coverage by smooth muscle cells, leading to a functional endothelial layer even after 10 to 14 days after stent implantation. A single layer of endothelial cells has been found to seal the neointima and thereby prevent the stimulus which facilitates and enhances the proliferation of cells beyond mere coverage of the foreign body.
The thinner the stent strut, the less the lumen of the stented vessel is obstructed. Moreover, a thin stent is more easily covered by a neoendothelial build-up. Accordingly, it is desirable to make the stent wall as thin as can be practically achieved. But the fluoroscopic visibility of stainless steel, for example, in a thickness below 60 μm is very poor because of the limited extinction of x-rays by such a thin metal tube.
Some improvement has been achieved by applying a suitable adherent material layer to stent core material of medical grade implantable 316L stainless steel. Layer materials have included gold and certain other noble metals, such as platinum. Such materials typically exhibit much greater radiopacity than stainless steel, that renders the stent highly visible under fluoroscopy as it is being advanced through the vessel lumen to the desired site of deployment, as well as after deployment. They are also substantially non-allergenic and non-thrombogenic. Such coating may be provided in a very thin layer, so the stent wall thickness is determined almost solely by considerations of mechanical strength. Coatings, however, present a need for absolute adherence to the underlying metal of the stent to avoid cracking or defects in the homogeneous overlying layer, and sufficient resistance to peeling or flaking of the layer during insertion, and especially during expansion of the diameter of the stent as it is being deployed in final position in the artery at the target site, objectives which are not easily achievable.
The disadvantage of reduced mechanical strength of noble metals such as gold or platinum—which makes them unsuitable if sought to be used alone for application in the human vascular system—is overcome by the use of a core composed of a material such as stainless steel, having considerably better mechanical properties than the noble metal. But the presence of cracks or related defects in the surface coating can produce a galvanic potential which could ultimately lead to corrosion of the underlying steel or lesser metal, an unacceptable situation for a device intended to be permanently implanted in the body. Therefore, manufacturing requires a high degree of quality control and concomitant high cost.
Alternative or additional layers have also been used in stents. Applicant's U.S. Pat. No. 6,099,561 discloses a stent structure having three fundamental layers, a first underlying layer of a base metal that functions to provide high mechanical strength, a second intermediate layer that functions to provide high fluoroscopic visibility—preferably a noble metal layer or alloy thereof—, and a top layer of a particularly beneficial biocompatible material—preferably a ceramic-like material such as iridium oxide or titanium nitrate. The intermediate layer of elemental or alloy of a noble metal is uninterrupted, highly adherent for tight coverage and substantially uniform thickness. Such an intermediate layer tends to assure avoidance of a galvanic potential that would lead to corrosion of the lesser, base metal, including such a condition that may obtain with a layer of ceramic-like metal overlying the base metal at points where fissures might exist were it not for the uninterrupted presence of the intermediate noble metal layer. The 3-layer stent of the '561 patent exhibits mechanical strength, small physical dimensions, increased visibility, long-term stability, and a highly biocompatible surface that enables rapid endothelialization with low occurrence of restenosis.
The '896 application, of which the present application is a continuation-in-part, discloses a stent adapted to be expanded from a first vessel-navigable diameter to a larger second vessel-deployed diameter, which is composed of material that possesses all of the desirable attributes mentioned above and yet can be fabricated in a single homogeneous structure without need for additional layers. The stent material is niobium, preferably with a sufficient amount of zirconium added, typically less than 5% by weight, for hardness of the combination. The stent may thus be fabricated from a single piece of tubing at relatively low cost and yet with all of the desirable features of non-allergenic reaction, excellent and adequate radiopacity (density twice that of stainless steel), distortionless for MRI, highly flexible, sufficiently elastic to be plastically deformable, non-brittle, sufficient strength to resist vessel recoil, and sufficient thinness to minimize obstruction to blood flow, and highly biocompatible. The niobium/zirconium material is anodized to provide surface oxidation. This material is readily treatable by post-processing such as annealing, electro-polishing for rounded edges, and so forth.
Additional surface modification or other substances or agents may be applied to the stent surface, such as vapor deposition of even more highly biocompatible layers, to preclude occlusion from restenosis or thrombosis during the acute stage following deployment of the stent. For example, iridium and iridium oxide, titanium nitrate, or compositions such as described in U.S. Pat. No. 5,679,815, might be applied.
The stent may also be formed from a sintering process with small microspheres by heat and pressure (e.g., such as disclosed in U.S. Pat. No. 5,198,187), thereby avoiding costly production and control steps.